Genetic risk of hyperuricemia in hypertensive patients associated with antihypertensive drug therapy: A longitudinal study.

Elevated serum uric acid (UA) level has been shown to be influenced by multiple genetic variants, but it remains uncertain how UA-associated variants differ in their influence on hyperuricemia risk in people taking antihypertensive drugs. We examined a total of 43 UA-related variants at 29 genes in 1840 patients with hypertension from a community-based longitudinal cohort during a median 2.25-year follow-up (including 1031 participants with normal UA, 440 prevalent hyperuricemia at baseline, and 369 new-onset hyperuricemia). Compared with the wild-type genotypes, patients carrying the SLC2A9 rs3775948G allele or the rs13129697G allele had decreased risk of hyperuricemia, while patients carrying the SLC2A9 rs11722228T allele had increased risk of hyperuricemia, after adjustment for cardiovascular risk factors and correction for multiple comparisons; moreover, these associations were modified by the use of diuretics, ß-blockers, or angiotensin converting enzyme inhibitors. The rs10821905A allele of A1CF gene was associated with increased risk of hyperuricemia, and this risk was enhanced by diuretics use. The studied variants were not observed to confer risk for incident cardiovascular events during the follow-up. In conclusion, the genes SLC2A9 and A1CF may serve as potential genetic markers for hyperuricemia risk in relation to antihypertensive drugs therapy in Chinese hypertensive patients.

Do we AGREE on the targets of antihypertensive drug treatment in older adults: a systematic review of guidelines on primary prevention of cardiovascular diseases.

BACKGROUND: translation of the available evidence concerning primary cardiovascular prevention into clinical guidance for the heterogeneous population of older adults is challenging. With this review, we aimed to give an overview of the thresholds and targets of antihypertensive drug therapy for older adults in currently used guidelines on primary cardiovascular prevention. Secondly, we evaluated the relationship between the advised targets and guideline characteristics, including guideline quality. METHODS: we systematically searched PubMed, Embase, Emcare and five guideline databases. We selected guidelines with (i) numerical thresholds for the initiation or target values of antihypertensive drug therapy in context of primary prevention (January 2008-July 2020) and (ii) specific advice concerning antihypertensive drug therapy in older adults. We extracted the recommendations and appraised the quality of included guidelines with the AGREE II instrument. RESULTS: thirty-four guidelines provided recommendations concerning antihypertensive drug therapy in older adults. Twenty advised a higher target of systolic blood pressure (SBP) for octogenarians in comparison with the general population and three advised a lower target. Over half of the guidelines (n = 18) recommended to target a SBP <150 mmHg in the oldest old, while four endorsed targets of SBP lower than 130 or 120 mmHg. Although many guidelines acknowledged frailty, only three gave specific thresholds and targets. Guideline characteristics, including methodological quality, were not related with the recommended targets. CONCLUSION: the ongoing debate concerning targets of antihypertensive treatment in older adults, is reflected in an inconsistency of recommendations across guidelines. Recommended targets are largely set on chronological rather than biological age.

Managing Hypertension in Patients Aged 75 Years and Older.

On the basis of the available data, we would diagnose a normal blood pressure in elderly persons including those 75 years of age and older if the blood pressure was below 120/80 mmHg. We would diagnose hypertension in elderly persons including those aged 75 years and older if the systolic blood pressure was 130 mmHg and higher or if the diastolic blood pressure was 80 mmHg and higher. We would treat these elderly patients with hypertension to a blood pressure goal of less than 130/80 mmHg if the blood pressure was obtained by automated blood pressure monitoring in a quiet room. We would consider treating high-risk persons aged 75 years and older to a blood pressure goal of less than 120/80 mmHg if they were carefully monitored for serious adverse events. If the blood pressure is more than 20/10 mmHg above the goal blood pressure, we would initiate antihypertensive drug therapy with two antihypertensive drugs. The initial drug of choice for the treatment of hypertension in adults aged 75 years and older should be based on co-morbidities, co-incidental indications, tolerability, and cost.

Managing Hypertension in the Elderly: What is Different, What is the Same?

PURPOSE OF REVIEW: The goal is to discuss management of hypertension in the elderly. RECENT FINDINGS: At 3.14-year follow-up of 2636 persons ≥75 years in the Systolic Blood Pressure Intervention Trial (SPRINT), compared with a systolic blood pressure (SBP) goal of <140 mmHg, a SBP goal of <120 mmHg reduced the primary endpoint of myocardial infarction, other acute coronary syndrome, stroke, heart failure, or cardiovascular death by 34% (p = 0.001), all-cause mortality by 33% (p = 0.009), heart failure by 38% (p = 0.003), and the primary outcome or death by 32% (p < 0.001). Absolute cardiovascular event rates were lower for the intensive treatment group within each frailty stratum. The incidence of serious adverse events was similar in both treatment groups. The SPRINT trial provides very important information on the efficacy and safety of lowering the SBP to <120 mmHg in elderly adults with hypertension.

African Ancestry vs. Creatine Kinase to Predict Hypertension Control: Time for a Change?

BACKGROUND: African ancestry patients are considered separately in hypertension guidelines because of more severe hypertension that is presumably harder to control. However, despite the perceived benefit in reducing health disparities, racial profiling in medicine is increasingly criticized for its potential of bias and stereotyping. Therefore, we studied whether creatine kinase (CK), an ATP-regenerating enzyme that enhances vascular contractility and sodium retention, could serve as a more proximate causal parameter of therapy failure than race/ancestry. METHODS: In a random multiethnic population sample, we compared the performance of African ancestry vs. resting plasma CK as predictors of treated uncontrolled hypertension. Difference in area under the receiver operating curve (AUC) was the primary outcome. RESULTS: We analyzed 1,405 persons of African, Asian, and European ancestry (40.2% men, mean age 45.5 years, SE 0.2). Hypertension prevalence was 39% in African vs. 29% in non-African ancestry participants vs. 41% and 27% by high and low CK tertiles. Control rates of treated patients were similar by ancestry (African ancestry patients 40%, non-African ancestry 41%; P = 0.84), but 27% vs. 53% in patients with high vs. low CK (22% vs. 67% in African and 32% vs. 52% in non-African participants). AUC was 0.51 [0.41-0.60] for African ancestry vs. 0.64 [0.55-0.73] for log CK (P = 0.02). CONCLUSIONS: In contrast to African ancestry, CK might identify hypertensive patients at risk for therapy failure across different ancestry groups. Larger, prospective studies should establish whether resting plasma CK is clinically useful as an impartial method to help predict antihypertensive therapy failure.

Pharmacological management of hypertension in the elderly and frail populations.

INTRODUCTION: Cardiovascular disease is a leading cause of mortality in the elderly. Hypertension is an important modifiable risk factor that contributes to cardiovascular morbidity and mortality. The prevalence of hypertension is known to increase with age, and hypertension has been associated with an increase in risk for cardiovascular disease in the elderly. There is a wealth of evidence that supports aggressive control of blood pressure to lower cardiovascular risk in the general population. However, there are limited data to guide management of hypertension in the elderly and frail patient subgroups. These subgroups are inadequately treated due to lack of clarity regarding blood pressure thresholds, treatment targets, comorbidities, frailty, drug interactions from polypharmacy, and high cost of care. Areas covered: We review the current evidence behind the definition, goals, and treatments for hypertension in the elderly and frail and outline a strategy that can be used to guide antihypertensive pharmacotherapy in this population. Expert commentary: Lower blood pressure to < 130/80 mm Hg in elderly patients if tolerated and promote use of combination therapy if the blood pressure is > 20/10 mm Hg over the goal blood pressure. Antihypertensive treatment regimens must be tailored to each individual based on their comorbidities, risk for adverse effects, and potential drug interactions ( Figure 1 ).

Comparison of Blood Pressure Control Rates Among Recommended Drug Selection Strategies for Initial Therapy of Hypertension.

BACKGROUND: Several approaches to initiation of antihypertensive therapy have been suggested. These include thiazide diuretics (TDs) as the first drug in all patients, initial drug selection based on age and race criteria, or therapy selection based on measures of plasma renin activity (PRA). It is uncertain which of these strategies achieves the highest control rate with monotherapy in Stage-I hypertension. We sought to compare control rates among these strategies. METHODS: We used data from the Pharmacogenomic Evaluation of Antihypertensive Responses study (PEAR) to estimate control rates for each strategy: (i) TD for all, (ii) age- and race-based strategy: Hydrochlorothiazide (HCTZ) for all blacks and for whites ≥50 years and a renin-angiotensin system inhibitor (atenolol) for whites <50 years) or (iii) a PRA based strategy: HCTZ for suppressed PRA (<0.6ng/ml/h) and atenolol for non-suppressed PRA (≥0.6ng/ml/h) despite age or race. Hypertension was confirmed prior to treatment with HCTZ (148 blacks and 218 whites) or with atenolol (146 blacks and 221 whites). RESULTS: In the overall sample, using clinic blood pressure (BP) response, the renin-based strategy was associated with the greatest control rate (48.9% vs. 40.8% with the age and race-based strategy (P = 0.0004) and 31.7% with the TD for all strategy (P < 0.0001)). The findings were similar using home or by 24-hour ambulatory BP responses and within each racial subgroup. CONCLUSIONS: A strategy for selection of initial antihypertensive drug therapy based on PRA was associated with greater BP control rates compared to a thiazide-for-all or an age and race-based strategy.

Dynamic view on affordability of fixed-dose combination antihypertensive drug therapy.

BACKGROUND: The use of fixed-dose combinations (FDCs) has been increasing since the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommended using ≥2 drugs as the first-line drug therapy for patients with stage 2 hypertension. FDCs simplify the drug therapy regimen and reportedly lower the drug therapy cost compared with the free combination (FC) of 2 single-agent drugs. This study hypothesized that the affordability of FDCs over FCs would change over time depending on the availability of generic single-agent drugs. METHODS: This study used the 2009 Medical Expenditure Panel Survey. Antihypertensive drugs were identified based on the Food and Drug Administration national drug directory. Based on the 2 databases, regression models were run to predict average monthly drug cost as well as out-of-pocket cost for each prescription along with their 95% confidence intervals (CIs). RESULTS: Overall, FDCs (n = 26) had average monthly drug costs similar to respective FCs when FCs were not generically available. However, when FCs were generically available, FDCs (n = 11) had average drugs costs much higher than their respective FCs. For example, Lotrel as an FDC had an average monthly drug cost of $115.97 (95% CI = $96.59-$135.36), whereas its counterpart FC had an average monthly drug cost of $21.00 (95% CI = $18.23-$23.79). CONCLUSIONS: The cost advantage of FDCs over FCs was reversed when FCs were generically available. The finding of this study informs patients, health-care providers, and drug plans of the importance of making dynamic decisions on preferred drug therapy options depending on the availability of generic drugs.

Adherence to antihypertensive medications and health outcomes among newly treated hypertensive patients.

OBJECTIVE: To evaluate adherence to antihypertensive therapy (AHT) and the association between adherence to AHT, all-cause mortality, and cardiovascular (CV) morbidity in a large cohort of patients newly treated with antihypertensives in a clinical practice setting. METHODS: An administrative database kept by the Local Health Unit of Florence (Italy) listing patient baseline characteristics, drug prescription, and hospital admission information was used to perform a population-based retrospective study including patients newly treated with antihypertensives, ≥18 years of age, with a first prescription between January 1, 2004 and December 31, 2006. Patients using antihypertensives for secondary prevention of CV disease, occasional spot users, and patients with early CV events, were excluded from the study cohort. Adherence to AHT was calculated and classified as poor, moderate, good, and excellent. A Cox regression model was conducted to determine the association among adherence to AHT and risk of all-cause mortality, stroke, or acute myocardial infarction. RESULTS: A total of 31,306 patients, 15,031 men (48.0%), and 16,275 women (52.0%), with a mean age of 60.2 ± 14.5 years was included in the study. Adherence to AHT was poor in 8038 patients (25.7% of included patients), moderate in 4640 (14.8%), good in 5651 (18.1%), and excellent in 12,977 (41.5%). Compared with patients with poor adherence (hazard ratio [HR] = 1), the risk of all-cause death, stroke, or acute myocardial infarction was significantly lower in patients with good (HR = 0.69, P < 0.001) and excellent adherence (HR = 0.53, P < 0.001). CONCLUSIONS: These findings indicate that suboptimal adherence to AHT occurs in a substantial proportion of patients and is associated with poor health outcomes already in primary prevention of CV diseases. For health authorities, this preliminary evidence underlines the need for monitoring and improving medication adherence in clinical practice.